Photodynamic Therapy (PDT) is presently undergoing extensive basic, pre-clinical, and clinical investigation for the diagnosis and treatment of cancer.The majority of this work has involved various versions of Hematoporphyrin Derivative (HpD) with the most recent purified version, Dihematoporphyrin Ether/Ester (DHE or PhotofrinR) involved in clinical trials.In 1982 Spears et al reported the selective uptake of HpD in atheromatous plaques. Since that time others (Spokojny et al, Litvack et al, Pollock et al, and Kessel et al) have confirmed and better characterized this phenomenon. It is the goal of this research to exploit the selective uptake by atherosclerotic plaque of newer "second generation" photosensitizers to diagnose and treat cardiovascular disease. So called second generation photosensitizers appear to have a greater selectivity in neoplastic tissue than their predecessor without the prolonged inherent skin photosensitivity. Phase I of this project will look at the uptake ratios (atheroma/healthy vessel) of two second generation photosensitizers and HpD as a control with the use of a fluorescence probe. Phase II will address the diagnosis and treatment of cardiovascular disease with a delivery device (patent pending) designed specifically for Photoatherolytic (PAL) Therapy.PAL Therapy as an adjunct to Percutaneous Transluminal Coronary Angioplasty (PTCA) has the potential to reduce the reported restenosis rate (40 percent) substantially through selective photochemolysis and may also have potential as a stand alone procedure for early diffuse disease. The potential of the diagnostic application is a guidance system for interventional therapies and to facilitate the decision making process of the clinician.